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Updated: Sep 1, 2025
Author Spotlight: Using Zebrafish to Explore Microglia Migration During Brain Development
Published on: May 17, 2024
The spatiotemporal dynamics of microglia across the human lifespan
David A Menassa1, Tim A O Muntslag2, Maria Martin-Estebané2
1School of Biological Sciences, University of Southampton, Southampton, United Kingdom; Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
Abstract:
Microglia, the brain's resident macrophages, shape neural development and are key neuroimmune hubs in the pathological signatures of neurodevelopmental disorders. Despite the importance of microglia, their development has not been carefully examined in the human brain, and most of our knowledge derives from rodents. We aimed to address this gap in knowledge by establishing an extensive collection of 97 post-mortem tissues in order to enable quantitative, sex-matched, detailed analysis of microglia across the human lifespan. We identify the dynamics of these cells in the human telencephalon, describing waves in microglial density across gestation, infancy, and childhood, controlled by a balance of proliferation and apoptosis, which track key neurodevelopmental milestones. These profound changes in microglia are also observed in bulk RNA-seq and single-cell RNA-seq datasets. This study provides a detailed insight into the spatiotemporal dynamics of microglia across the human lifespan and serves as a foundation for elucidating how microglia contribute to shaping neurodevelopment in humans.
Insights
Human microglia development was mapped across the lifespan, revealing dynamic changes in cell density during gestation, infancy, and childhood. These findings offer insights into neurodevelopment and neuroimmune disorders.
Area of Science:
- Neuroscience
- Immunology
- Developmental Biology
Background:
- Microglia, the brain's resident macrophages, are crucial for neural development and neuroimmune processes.
- Current understanding of microglial development heavily relies on rodent models, with limited data from the human brain.
- The developmental trajectory of human microglia across the lifespan remains largely uncharacterized.
Purpose of the Study:
- To comprehensively analyze the development and lifespan dynamics of microglia in the human brain.
- To establish a quantitative, sex-matched dataset of human microglia across different life stages.
- To correlate microglial changes with key neurodevelopmental milestones.
Main Methods:
- Analysis of 97 post-mortem human telencephalon tissues.
- Quantitative, sex-matched histological analysis of microglial density.
- Examination of microglial proliferation and apoptosis rates.
- Integration with bulk and single-cell RNA sequencing data.
Main Results:
- Detailed mapping of microglial density dynamics throughout human gestation, infancy, and childhood.
- Identification of distinct waves of microglial proliferation and apoptosis correlating with neurodevelopmental stages.
- Confirmation of observed microglial changes through transcriptomic analyses (bulk and single-cell RNA-seq).
Conclusions:
- This study provides the first extensive, lifespan-based characterization of human microglial development.
- The findings reveal critical spatiotemporal dynamics of microglia that track human neurodevelopment.
- This work establishes a foundational resource for understanding microglia's role in human neurodevelopment and disorders.
